Ansprechen eines BRAFL597Q-mutierten Melanoms auf Trametinib

Haase, Ozan; Angün, O.; Grätz, Victoria; Lüttmann, Nadine; Neumann, Alexander; Zillikens, Detlef; Terheyden, Patrick

doi:10.1007/s00105-016-3785-3

Cited by 2 publications

(1 citation statement)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…reported a BRAF L597R ‐mutated melanoma that was responsive to vemurafenib treatment . In the third investigated subset of BRAF L597 ‐mutated melanoma, and in particular the BRAF L597Q mutation, three patients have been described: two responded to trametinib and one had no response to vemurafenib …”

Section: High‐kinase‐activity Braf Mutationsmentioning

confidence: 99%

Beyond the BRAF ^V ^600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients

et al. 2017

View full text Add to dashboard Cite

BRAF gene mutations can be found in approximately 50% of melanomas, but the most common BRAF mutation leads to substitution at residue 600 of the protein, from valine to glutamic acid. BRAF occurs in up to 95% of all melanoma cases and can be successfully blocked by using a combination of BRAF- and MEK inhibitors. The wider availability of next-generation sequencing is revealing more non-V600 BRAF mutations, and the clinical implications of these mutations are widely unknown. In this review, we will discuss the biology of the MAPK pathway and the different types of BRAF mutations as well as their effect on MEK activation. Current literature will be reviewed including in vitro data, case reports and case series.

show abstract

Section: High‐kinase‐activity Braf Mutationsmentioning

confidence: 99%

Beyond the BRAF ^V ^600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients

et al. 2017

View full text Add to dashboard Cite

show abstract

Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations

et al. 2018

View full text Add to dashboard Cite

The RAS-RAF-MEK-ERK signaling cascade is among the most frequently mutated pathways in human cancer. Approximately 50% of melanoma patients possess a druggable hotspot V600E/K mutation in the BRAF protein kinase. FDA-approved combination therapies of BRAF and MEK inhibitors are available that provide survival benefits to patients with a BRAF V600 mutation. Non-V600 BRAF mutants are found in many cancers, and are more prevalent than V600 mutations in certain tumor types. For example, between 50-80% of BRAF mutations in non-small cell lung cancer and 22-30% in colorectal cancer encode for non-V600 mutants. As next generation sequencing becomes increasingly used in clinical practice, oncologists are frequently identifying non-V600 BRAF mutations in their patient's tumors, but are uncertain of viable therapeutic options that could be employed for optimal treatment. From recent studies, a new classification system is emerging for BRAF mutations based on biochemical and signaling mechanisms associated with these mutants. Class I BRAF mutations affect amino acid V600 and signal as RAS-independent active monomers, class II mutations function as RAS-independent activated dimers, and class III mutations are kinase impaired but increase signaling through the MAPK pathway due to enhanced RAS binding and subsequent CRAF activation. These distinct classes of BRAF mutations predict response to targeted therapies and have important implications for future drug development. Herein, we discuss pre-clinical and clinical findings that may lead to improved treatments for all classes of BRAF mutant cancers.

show abstract

Ansprechen eines BRAFL597Q-mutierten Melanoms auf Trametinib

Cited by 2 publications

References 10 publications

Beyond the BRAF ^V ^600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients

Beyond the BRAF ^V ^600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients

Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations

Contact Info

Product

Resources

About

Ansprechen eines BRAFL597Q-mutierten Melanoms auf Trametinib

Cited by 2 publications

References 10 publications

Beyond the BRAF V 600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients

Beyond the BRAF V 600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients

Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations

Contact Info

Product

Resources

About

Beyond the BRAF ^V ^600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients

Beyond the BRAF ^V ^600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients